We report a case of reversible hypertriglyceridemia in a patient receiving -interferon for chronic hepatitis C infection. A 36-year-old man with diabetes mellitus who was receiving oral glyburide, 10 mg daily, was started on 3 million units of subcutaneous -interferon, thrice weekly. The patient was hepatitis C seropositive, and a liver biopsy showed chronic, active hepatitis. His baseline serum triglyceride level was 3.8 mmol/L (340 mg/dL), and his serum cholesterol level was 5.7 mmol/L (220 mg/dL). After the first week of interferon therapy, the patient's serum lipids rose to a peak of 22.4 mmol/L (1980 mg/dL) and 9.1 mmol/L (354 mg/dL), respectively (Figure 1). The patient was asymptomatic, and a serum amylase level was normal. During this period, his blood glucose ranged from 8.8 to 14.4 mmol/L (159 to 259 mg/dL). Treatment was discontinued after 4 weeks, and the triglyceride level declined (see Figure 1). At week 8, after reinstitution of the same dose of -interferon, the triglyceride level increased threefold. Because the patient was reluctant to stop therapy altogether, oral gemfibrozil, 1200 mg daily, was started on week 10. Despite blunting the rise in serum triglyceride, the effect was judged inadequate, and interferon and gemfibrozil therapy were stopped. Shortly after the withdrawal of both medications, the patient's triglyceride level returned to near baseline.

View larger version (20K): [in this window] [in a new window]   Figure 1. Lipid profile in a 36-year-old man treated with -interferon for chronic hepatitis C. IF = interferon; TG = triglycerides.

Alpha-interferon, a cytokine known to affect lipid metabolism [1] at doses used in the treatment of hepatitis C, can cause a 0.7-mmol/L (62 mg/dL) median increase in serum triglyceride levels [2]. Feingold and colleagues [1] showed that -interferon (but not ß –or -interferon) rapidly stimulates de-novo hepatic fatty acid synthesis in mice. In humans, circulating levels of endogenous -interferon and serum triglyceride have been found to correlate directly in patients seropositive for human immunodeficiency virus (HIV) [3]. In this series, high interferon levels were associated with high triglyceride levels that peaked at 13.1 mmol/L (1161 mg/dL).

The rechallenge period and the return of triglyceride levels to baseline after cessation of -interferon therapy favor a direct causal relation. Monitoring of serum triglycerides during interferon therapy may be warranted to avert the potentially severe complications of hypertriglyceridemia.